Background: The present study identified, quantified, and characterized the combinations of phytocomponents from fractionated leaf extracts of Anacardium occidentale, Psidium guajava, and Terminalia catappa that stabilized sickle erythrocyte membrane against osmotic stress, or otherwise, using standard chromatographicspectrophotometric techniques, namely GC-MS, FT-IR, and UV-visible systems. Results: The percentage hemolysis of the control sample, in 0.9 g/100 mL NaCl, was 35.08 ± 11.64%, whereas those of the samples containing 40 mg/100 mL, 60 mg/100 mL, and 80 mg/100 mL of ethylacetate extracts of T. catappa ranged between 31.82 ± 8.32 and 39.18 ± 6.94%. Ethylacetate extract of T. catappa contained comparative high quantities of hexadecanoic acid methyl ester, 9,11-octadecadienoic acid, methyl ester, (E, E)-, trans-13-octadecenoic acid methyl ester, and methyl stearate. FT-IR and UV-visible spectra showed that ethylacetate extract of T. catappa contained aromatic compounds as well as nitro-compounds, phenolics, and esters. Conclusion: To mention but a few, the combinations of major phytocomponents that stabilized sickle erythrocyte membrane against osmotic stress were hexadecanoic acid, methyl ester, 11-octadecenoic acid, methyl ester, dibutyl phthalate, pentacosane, trans-13-octadecenoic acid, methyl ester, whereas the minor phytocomponents include methyl tetradecanoate, methoxyacetic acid, 3-pentadecyl ester, methyl stearate, hexadecanoic acid, isoxazole, 4,5-dimethyl-.